Hamburg: FDA Crackdown on Quality Compliance Coming

By Mari SerebrovWashington Editor

Provided budget constraints don't derail the FDA's plans, the agency is on track to begin conducting biennial inspections of all drug facilities, both domestic and foreign, in five years, according to FDA Commissioner Margaret Hamburg.

That goal is within reach thanks to new and increased user fees included in the FDA Safety and Innovation Act passed last year. Since its implementation in October 2012, the new generic drug user fee has resulted in 2,000 generic facilities being registered with the FDA and has generated $125 million for the agency, Hamburg told drugmakers attending the annual meeting of the Generic Pharmaceutical Association Friday.

There is a catch. The continuing resolution Congress passed last fall in lieu of a budget restricts the FDA's spending to that of fiscal 2012. While Congress later passed an amendment allowing the agency to use the new generic drug fees, the FDA's ability to spend new dollars is still limited, Hamburg said. (See BioWorld Today, Sept. 21, 2012, and Oct. 9, 2012.)

The sequester that's slated to kick in March 1 also could cut deeply into the agency's resources, further delaying its ability to conduct biennial facility inspections in other countries.

The infrequency of foreign inspections has long been a sore point with Congress and domestic drugmakers, who, by law, must have their facilities inspected every two years. Yet 80 percent of the active pharmaceutical ingredients used in U.S. drugs and 40 percent of finished drug products are made outside the U.S., many of them at facilities that have never been inspected. (See BioWorld Today, Sept. 15, 2011.)

Testifying in a House subcommittee hearing last year on generic drug and biosimilar user fees, Heather Bresch, CEO of Mylan Inc., noted that foreign facilities supporting the U.S. drug supply have grown by 185 percent while at the same time, the FDA inspection rates have decreased by nearly 57 percent. (See BioWorld Today, Feb. 13, 2012.)

Besides leveling competition, putting everyone on a biennial inspection cycle would strengthen the FDA's continued focus on quality, making compliance with good manufacturing practices all the more necessary for brand and generic drugmakers, as well as compounding pharmacies. "All segments of the pharmaceutical industry must embrace quality manufacturing," Hamburg warned drugmakers.

The agency isn't looking at imposing new quality requirements, but it is cracking down on compliance with the existing standards, she added, citing a long list of recent manufacturing problems that have led to recalls and facility closures. Problems such as glass fragments in sterile injectables or prescription drugs being mixed in with over-the-counter medicines are "all warning signals that we can and must do more," Hamburg said.

To prevent such manufacturing problems in the future, drugmakers should build quality into their processes by creating redundancies, developing contingency plans and upgrading old facilities. "This will be money well spent," Hamburg said, as it will, in the long run, allow for more regulatory flexibility.

It also will maintain public confidence in generic drugs, she said, reminding the generic companies of the struggle they faced years ago in convincing doctors and patients that generics were equivalent to brand drugs. It takes only a few lapses in quality to undo that reputation, she added.

Trust also will be an issue with biosimilars. "Efforts to undermine trust in these products are worrisome," Hamburg said, without elaboration.

While the FDA has yet to receive a biosimilar application, it is ready and eager to begin the approval process, she said. In the meantime, the agency is moving forward with finalizing three draft biosimilar guidances released last year. (See BioWorld Today, Feb. 10, 2012.)

FDA Finalizes Labeling Guidance

Makers of drugs and biologics now have final guidance on the physician labeling rule (PLR) the FDA issued more than seven years ago.

The latest in a series of guidances on labeling, the new guidance, published in Monday's Federal Register, provides recommendations for developing labeling for new drugs and revising labeling for drugs already on the market. It also includes recommendations on developing highlights of prescribing information, formatting labeling and procedural information.

While the PLR has been in effect for new drugs, labeling revisions for drugs that were already approved are being implemented in stages. As of last summer, the labeling for all drugs approved on or after June 30, 2002, had to be revised in accordance with the PLR.

By June 30 of this year, all drugs that were approved on or after June 30, 2001, must have the revised labeling. Changes for drugs approved before that date are voluntary and can be made at any time.

In addition to the labeling guidance, the FDA issued a draft guidance on how sponsors should submit hepatitis C virus resistance data from trials of direct-acting antivirals. Comments on the draft, which also was published in Monday's Federal Register, are due by April 26.